The objective of this project is the development of gamma ray emitting radiodiagnostic agents which can noninvasively detect, localize and characterize estrogen receptor-containing breast tumors in women. The specific aims include the synthesis of several series of halogen- or selenium-containing estrogens and antiestrogens, the evaluation in vitro of their affinity for specific receptors, the determination in vivo of their specific uptake in estrogen receptor containing organs and tumors, and the study of the ability of these agents in combination with the gamma scintillation camera to visualize noninvasively these tissues in laboratory animals. The synthesis of the unlabeled and radiolabeled target compounds utilizes organotin methodology developed in our laboratories which enhances both the regiospecificity of the last synthetic step and the ease of isolation of the product. Receptor affinity determinations will use both indirect (cold ligand versus 3H-estradiol) and direct (radioligand versus cold estradiol) methods. Specific receptor binding will be assayed by sucrose gradient analysis. The in vivo studies in small animals will employ the immature female rat uteri and DMBA-induced rat mammary carcinoma as the model systems. The pharmacokinetic and metabolic evaluations of the radioligands, as well as the external studies, will be conducted in female dogs.